Culture

Although plexiglass barriers are seemingly everywhere these days -- between grocery store lanes, around restaurant tables and towering above office cubicles -- they are an imperfect solution to blocking virus transmission.

Instead of capturing virus-laden respiratory droplets and aerosols, plexiglass dividers merely deflect droplets, causing them to bounce away but remain in the air. To enhance the function of these protective barriers, Northwestern University researchers have developed a new transparent material that can capture droplets and aerosols, effectively removing them from air.

The material is a clear, viscous liquid that can be painted onto any surface, including plastic, glass, wood, metal, stainless steel, concrete and textiles. When droplets collide with the coated surface, they stick to it, get absorbed and dry up. The coating also is compatible with antiviral and antimicrobial materials, so sanitizing agents, such as copper, could be added to the formula.

"Droplets collide with indoor surfaces all the time," said Northwestern's Jiaxing Huang, the study's senior author. "Right now, plexiglass dividers are deviating devices; they deflect droplets. If a surface could actually trap droplets, then every single droplet effectively removed from indoor air would be a successful elimination of a potential source of transmission."

The research will be published Wednesday (June 16) in the journal Chem. In the study, the researchers found that even when they bombarded surfaces with aerosol droplets -- at orders of magnitude higher concentration than typical for an indoor environment -- the coated surfaces still captured three times more aerosol droplets than uncoated surfaces.

Huang is a professor of materials science and engineering in Northwestern's McCormick School of Engineering. Zhilong Yu, Murak Kadir and Yihan Liu -- all members of Huang's laboratory -- co-authored the paper. The team embarked on this project during the stay-at-home order at the beginning of the pandemic.

The main ingredient in the Northwestern team's material is a polyelectrolyte polymer that is commonly used in a wide variety of cosmetic products. When applied with a blade or brush, the resulting formula yields uniform and conformal coatings on a broad range of indoor surfaces without damaging or discoloring the original material.

Huang's team found the surfaces also remained transparent and haze-free even when doused with droplets. In other words, the surfaces did not appear filthy or soiled after being showered with droplets. If used on plexiglass barriers, those coated barriers would not need to be cleaned more frequently than uncoated barriers.

Most infectious diseases spread through respiratory droplets and aerosols, which humans release constantly when talking, laughing, singing and exhaling. Because the coating is so versatile, Huang imagines that it could be used on plexiglass barriers and face shields as well as on no-touch or low-touch surfaces, such as walls or even curtains, to eliminate those droplets from the air.

"There are massive areas of indoor surfaces that are barely touched by people or pets. If we repurposed these 'idling' surfaces to capture respiratory droplets, then they could become functional 'devices' to help reduce air-borne transmission of infectious diseases," he said. "Surface-trapped pathogens can then be readily inactivated over time, which can be accelerated by pre-applied sanitization ingredients. They also can be removed during routine cleaning."

While Huang says that face masks are an irreplaceable public health tool to help preventing the spread of infectious droplets, he believes that trapping droplets on surfaces could be another effective tool.

"In a computer game, for example, you don't want to walk into a battlefield with only one piece of armor," he said. "It makes sense to leverage multiple layers of defense."

New York, NY (June 16, 2021) -- Immune cells that normally repair tissues in the body can be fooled by tumors when cancer starts forming in the lungs and instead help the tumor become invasive, according to a surprising discovery reported by Mount Sinai scientists in Nature in June.

The researchers found that early-stage lung cancer tumors coopt the immune cells, known as tissue-resident macrophages, to help invade lung tissue. They also mapped out the process, or program, of how the macrophages allows a tumor to hurt the tissues the macrophage normally repairs. This process allows the tumor to hide from the immune system and proliferate into later, deadly stages of cancer.

Macrophages play a key role in shaping the tumor microenvironment, the ecosystem that surrounds tumors in the body. By investigating this microenvironment, researchers can find key players that drive tumor growth that can be tested as targets for immunotherapy. But modifying macrophages therapeutically has proven difficult.

In this study, scientists studied tissue samples from lung cancer tumors and surrounding lung tissue in 35 patients to see the role of macrophages in the development of the tumors.

The study's lead author, Miriam Merad, MD, PhD, Director of the Precision Immunology Institute at the Icahn School of Medicine at Mount Sinai, and a multidisciplinary team of thoracic surgeons, pathologists, and medical oncologists within the Institute of Thoracic Oncology devised a comprehensive study that began when patients went into surgery to have cancerous lesions removed. The patients' lung tumor samples, samples of surrounding healthy lung tissue, and blood samples were immediately analyzed on a cellular level at Mount Sinai's Human Immune Monitoring Center to map out the immune system components they contained.

Researchers identified the macrophages at play in the early development of lung cancer, identifying a potential target for future drug development. They also found that the process that allows the macrophages to help tumors invade lung tissues is present in mice as well, which will allow them to manipulate the macrophages in future mouse models knowing that the manipulation is relevant to humans.

Half of all early-stage lung cancers relapse, and once they do and reach later stages, it is deadly and irreversible. Knowing how to attack the cancer at an early stage could have huge impacts on the number of patients relapsing and their overall survival.

"These findings are very important for Mount Sinai in the future as we have a very strong lung cancer screening program that identifies patients with early lung cancer lesions before they become fully invasive," said Dr. Merad, who is also the Director of the Human Immune Monitoring Center and a member of the Institute of Thoracic Oncology and The Tisch Cancer Institute at Mount Sinai. "These findings will help devise immunoprevention strategies to prevent tumor progression in patients at risk by reprogramming macrophages and killing the tumor without surgery."

It sounds like a plot from a Quentin Tarantino movie -- something sets off natural killers and sends them on a killing spree.

But instead of characters in a movie, these natural killers are part of the human immune system and their targets are breast cancer tumor cells. The triggers are fusion proteins developed by Clemson University researchers that link the two together.

"The idea is to use this bifunctional protein to bridge the natural killer cells and breast cancer tumor cells," said Yanzhang (Charlie) Wei, a professor in the College of Science's Department of Biological Sciences. "If the two cells are brought close enough together through this receptor ligand connection, the natural killer cells can release what I call killing machinery to have the tumor cells killed."

It's a novel approach to developing breast cancer-specific immunotherapy and could lead to new treatment options for the world's most common cancer.

About one in eight women in the U.S. and one in 1,000 men will develop invasive breast cancer during their lives. Breast cancer is the second leading cause of cancer death in women in the U.S., trailing only lung cancer. The American Cancer Society estimates that about 43,600 U.S. women will die from the disease this year.

Immunotherapy harnesses the power of the body's immune system to kill cancer cells.

"Very simply, cancer is uncontrolled cell growth. Some cells will become abnormal and have the potential to become cancer," Wei said. "The immune system can recognize these abnormal cells and destroy them before they become cancer cells. Unfortunately for those who develop cancer, the immune system is not working very well because of gene mutations and environmental factors. The result is that the cancer cells won the fight between the immune system and the tumors."

Most breast cancer targeting therapies target one of three receptors: estrogen receptors, progesterone receptors or epidermal growth factor receptors. However, up to 20 percent of breast cancers do not express these receptors. These cancers are known as triple-negative breast cancer. Triple-negative is the most lethal subtype of breast cancer because of high heterogeneity, high metastasis frequency, early relapse after standard chemotherapy and lack of efficient treatment options.

In this novel research, Wei and his researchers targeted prolactin receptors. Prolactin is a natural hormone in the body and plays a role in breast growth and milk production during breastfeeding. Breast cancer cells overexpress prolactin receptors.

"When people are diagnosed with breast cancer, and it's called triple-negative, it is not good news," Wei said. "This has the potential to give patients another option."

Over 90 percent of breast cancer cells express prolactin receptors, including triple-negative breast cancer cells.

Wei and his team developed a bifunctional protein. One part is a mutated form of prolactin that can still bind to the prolactin receptor but blocks signal transduction that would promote tumor growth. The other part is an extracellular domain of major histocompatibility complex class I chain-related protein (MICA).

When the MICA binds to the prolactin receptor, it activates the natural killer cells.

"One of the things tumor cells do is to inhibit natural killer cell activation, so we use these artificial bifunctional proteins to connect natural killer cells and activate them to enhance the killing of the breast cancer cells without increased cytotoxicity," Wei said.

Wei is now seeking funding for an animal model study to confirm the results.

One big question is whether the bifunctional protein will bring natural killer cells to healthy cells in the body that also express prolactin receptors and kill them, too, causing severe side effects.

If the animal model studies are successful, the potential new treatment could move to human clinical trials.

"If we had the funding now and everything is what we expected in the animal model study, we could be in clinical trials in five or six years," he said. Wei said he expects the conversion from in-vitro and animal studies to clinical trials to be easier for this potential immunotherapy than others in the past because the protein created by the Clemson researchers uses human natural killer cells and breast cancer cells.

Developing new immunotherapy for cancer is nothing new to Wei. His research combining tumor cells with dendritic cells, an important part of the body's adaptive immune system, led to a dendritoma vaccine that proved effective in melanoma, renal cell carcinoma and neuroblastoma patients. The vaccine was patented and licensed to three biotech companies. Two companies are still pursuing the vaccine therapy or related therapy.

"It is my dream that someday we can create a group of these bifunctional proteins that could be used for other cancers by shifting the target molecule. We'd have the one part of the bifunctional protein that targets natural killer cells. The other part would target other cancer types that have unique markers," Wei said.

A group of researchers from the University of Jyvaskyla and Stanford University were part of an expedition to French Guiana to study tropical frogs in the Amazon. Various amphibian species of this region use ephemeral pools of water as their nurseries, and display unique preferences for specific physical and chemical characteristics. Despite species-specific preferences, researchers were surprised to find tadpoles of the dyeing poison frog surviving in an incredible range of both chemical (pH 3-8) and vertical (0-20 m in height) deposition sites. This research was published in the journal Ecology and Evolution in June 2021.

Neotropical frogs are special because, unlike species in temperate regions, many tropical frogs lay their eggs on the ground. This becomes an issue once tadpoles (who breathe using gills, like fish) hatch onto the forest floor, but poison frogs have developed innovative solutions to get their tadpoles to suitable aquatic habitats: piggy-back rides. In many of these terrestrial-breeding species, fathers will transport recently hatched tadpoles from the ground to pools of water formed by vegetation (like fallen trees or bromeliads).

PhD researcher Chloe Fouilloux and team leaders Dr. Bibiana Rojas from University of Jyvaskyla, Finland and Dr. Andrius Pasukonis from Stanford University wanted to know if different species (Dendrobates tinctorius, Allobates femoralis, and Osteocephalus oophagus) considered a combination of biological, physical, or chemical characteristics of pools when choosing nurseries for their young.

To find that out, this group of eight researchers sampled more than 100 pools over two years, which involved searching for suitable deposition sites that ranged from the ground to over 20 meter in vertical height (reached by climbing trees).

Of the three species, range and tolerance of D. tinctorius (dyeing poison frog) tadpoles was beyond what any of the researchers imagined physiologically possible: healthy tadpoles were found in a range of pools with a pH of around 3 to a pH of 8, which represents a 100,000x change of hydrogen ion concentration; in other words, these tadpoles were successfully developing in pools of what is chemically more acidic than orange juice to pools that have similar ionic concentrations to sea water!

The deposition choices of dyeing poison frogs confused researchers in other ways, too: tadpoles of this species are aggressive cannibals, which is why they are usually found to occur in low densities (1-2 tadpoles) per pool.

"However, in this study, we found several instances of more than 10 tadpoles of this species coexisting in the same nursery. The reason why fathers would deposit so many cannibals within the same pool, or if cannibalism occurs within these special pools, has yet to be tested", says PhD researcher Chloe Fouilloux from University of Jyväskylä.

Healthier males transporting their tadpoles to more suitable conditions?

From a parental perspective, dyeing poison frog fathers were found to carry their tadpoles more than 20 meters above the forest floor: for a frog that is about 4 centimeter long, 20 meters is 500 times their body length. In human terms, this physical feat would be equivalent to having a 1.65 meter person climbing up a giant (non-existent, obviously) tree of about 825 meters!

But why do fathers sometimes carry their tadpoles one meter away from where they hatched, and other times transport them to the tops of trees?

When looking at the chemical and biological trends, it appears that more biologically "comfortable" nurseries are found higher in trees. One possible explanation for this finding is that healthier males are able to invest more energy in transporting their tadpoles to more suitable conditions, but this is something that would need to be investigated in the future. Ultimately, there remains a lot to be learnt about the physiology and parental care of these animals; the degree of chemical flexibility found in these tadpoles is extremely unusual, and the secret underlying their resilience remains unknown.

"This work helps highlighting the amazing diversity observed between and among species in the wild: parents from different species prioritise unique characteristics when choosing pools to raise their offspring, which shapes both how species interact with each other and how they specialize in occupying different parts of the environment", states Dr. Bibiana Rojas from University of Jyväskylä.

This variation opens the door to future research that explores how species influence each other and how pool choice by parents affects tadpole development and survival.

Chemokine receptors, located at the surface of many immune cells, play an important role in their function. Chemokines are small proteins that bind to these receptors and control the movement and behaviour of white blood cells. However, despite the importance of this family of receptors, their activation mechanism remains poorly understood. In Switzerland, a research consortium from the University of Geneva (UNIGE), the Biozentrum of the University of Basel, and the Paul Scherrer Institute (PSI) in Villigen has succeeded in decoding the activation mechanism of the CCR5 receptor, a member of this family implicated in several diseases such as HIV/AIDS, cancer, and the respiratory complications of COVID-19. This discovery represents an important step in the understanding of chemokine receptor biology, providing valuable insights for improving new drugs that this important family of receptors. This work can be found in the journal Science Advances.

The CCR5 receptor plays a major role in inflammation and immune defence, and has long been an important target for anti-HIV drugs. "Research on CCR5 began almost 25 years ago as part of the fight against AIDS", explains Stephan Grzesiek, a professor at the Biozentrum of the University of Basel, who co-directed this work with Professor Oliver Hartley of the Department of Pathology and Immunology at UNIGE Faculty of Medicine, and colleagues from the Paul Scherrer Institute (PSI). "It is indeed fundamental to the HIV infection mechanism, but also seems to be very important in many other pathological processes, notably in cancers and inflammatory diseases. However, in order to better exploit it for therapeutic purposes, we needed to understand, at an atomic level, how activation through its binding to chemokines works."

Chemokines are small signalling molecules that play a central role in the circulation and activation of immune cells. By binding to receptors on the membrane of white blood cells, they act as guides, ensuring that the cells reach the right place at the right time, to both maintain the immune system and respond to infection or injury. But how is the receptor able to sense the docking of a chemokine at the outside the cell? And how is this activation message transmitted to the inside of the cell so that it can respond?

Visualising atomic structures in 3D

Until now, the study of this phenomenon has been hampered by the difficulty of observing the 3D structures of the receptors when bound to the molecules that activate them. To this end, the Basel team, which specialises in structural biology, used cryo-electron microscopy tools that make it possible to preserve and observe the structure of the smallest elements of living organisms. "However, in order to understand the entire process, it is necessary to make use of engineered chemokines that bind to receptors more stably than the natural ones", says Oliver Hartley. "For this, we were able to exploit the molecules that we had discovered in the course of our HIV drug research." And indeed, some of these variants over-activate the receptor while others block them entirely.

The right key to fit in the lock

The receptor, which is embedded in the cell membrane, works like a "lock and key" mechanism. A specific part of the chemokine structure must fit into the CCR5 lock to activate a change in the structure of the receptor, which then lets it trigger the activation and migration of white blood cells. "The activation capacity of chemokines is determined by certain amino acids (protein building blocks) that must arrange themselves in a specific pattern. If this part of the chemokine adopts a straight shape, it succeeds in activating the receptor. But if the amino acids are changed, the molecule adopts a slightly different shape which, although it maintains a very strong bond with the receptor, prevents its activation", explains Oliver Hartley. These small changes thus make the difference between receptor activators and inhibitors.

Better-targeted and therefore more effective drugs

Despite an almost identical architecture, minute structural differences between engineered chemokines determine their ability to activate or inhibit the receptor. A detailed understanding of this mechanism will allow for the improvement of drugs by developing new compounds capable of fine-tuning the the immune system.

Research published today in the Journal of General Virology has identified missed cases of SARS-CoV-2 by retrospective testing of throat swabs.

Researchers at the University of Nottingham screened 1,660 routine diagnostic specimens which had been collected at a Nottingham hospital between 2 January and 11 March 2020 and tested for SARS-CoV-2 by PCR. At this stage of the pandemic, there was very little COVID-19 testing available in hospitals, and to qualify patients had to meet a strict criterion, including recent travel to certain countries in Asia or contact with a known positive case.

Three previously unidentified cases of SARS-CoV-2 infection were identified by the retrospective screening, including one from a 75-year-old female whose positive swab was collected on 21 February 2020. This patient, referred to as Patient 1, died on 3 March; two days before the first official death from COVID-19 was recorded in the UK. Patient 1 had not recently travelled abroad or been in contact with anyone known to have COVID-19 and so did not qualify for a PCR test at the time. In addition to being the first death, the researchers believe that Patient 1 is also the earliest described case of community transmission in the UK.

The further newly-identified cases occurred in a 64-year-old male and a 66-year-old male, both of whom showed signs of chest infections, and both of whom recovered. The samples were collected on 2 March and 8 March 2020 respectively. International travel was only removed as an essential criterion for a SARS-CoV-2 test on 12 March 2020.

The research group collaborated with the COVID-19 Genomics UK Consortium (COG-UK) to sequence the SARS-CoV-2 isolates collected from the swabs used in the study, and found evidence of community transmission in Nottingham as early as February 2020. Through this genome sequence data, the group identified multiple introductions of the virus into Nottingham during late February and the month of March, many of which were a distinct lineage of the virus which dominated early phases of the outbreak within the region.

Based on the findings, the researchers suggest that testing should have been made available to hospital patients with compatible symptoms but no travel history earlier in the pandemic response.

The full research article, 'Retrospective screening of routine respiratory samples revealed undetected community transmission and missed intervention opportunities for SARS-CoV-2 in the United Kingdom' is free to read in the Journal of General Virology (doi: 10.1099/jgv.0.001595).

Tokyo, Japan - Colloids--mixtures of particles made from one substance, dispersed in another substance--crop up in numerous areas of everyday life, including cosmetics, food and dyes, and form important systems within our bodies. Understanding the behavior of colloids therefore has wide-ranging implications, yet investigating the rotation of spherical particles has been challenging. Now, an international team including researchers from The University of Tokyo Institute of Industrial Science has created particles with an off-center core or "eye" that can be tracked using microscopy. Their findings are published in Physical Review X.

Particles suspended in a liquid move from one place to another as a result of Brownian motion, which can be easily detected with a microscope. However, these particles also rotate, which is much more difficult to see if they are spherical.

The researchers overcame this by creating particles made from two different colors of the same material. The core sphere--which they call the eye--is set off-center at the surface of the particle. It provides a point that can be followed under a microscope to determine the orientation changes as the particle rotates.

"The rotation of a colloidal particle tells us about the surrounding hydrodynamics--the motion of the suspending liquid--and the contact forces, such as friction. However, to get the full picture in a dense suspension, all of the particles must be tracked at once," explains study corresponding author Professor Hajime Tanaka. "As well as providing a point to track over time, the density and refractive index of our particles can be matched so that the necessary 3D images can be acquired."

By tracking a dense suspension of charged particles forming a colloidal crystal--which has an ordered arrangement of particles--it was found that the rotation of neighboring spheres was coupled and moved in opposite directions, like meshed gears.

In addition, a system with uncharged particles showed that there was a relationship between local crystallinity--the ordering in the immediate surroundings--and the rotational diffusivity, which describes the process of the orientation regaining equilibrium.

The researchers also observed "stick-slip" rotational motion between particles that make contact, where a large neighbor could stop the motion of a particle through friction.

"Our system has provided much-needed insight into hydrodynamic and frictional coupling in very dense colloids," says other corresponding author Professor Roel Dullens. "We expect our findings to have a significant impact on the design of industrial processes involving colloids, as well as on the understanding of biological processes."

ENVIRONMENT Diesel-polluted soil from now defunct military outposts in Greenland can be remediated using naturally occurring soil bacteria according to an extensive five-year experiment in Mestersvig, East Greenland, to which the University of Copenhagen has contributed.

Mothballed military outposts and stacks of rusting oil drums aren't an unusual sight in Greenland. Indeed, there are about 30 abandoned military installations in Greenland where diesel, once used to keep generators and other machinery running, may have seeped into the ground.

This is the case with Station 9117 Mestersvig, an abandoned military airfield on the coast of East Greenland. Forty tons of diesel fuel contaminated the soil at Mestersvig. As a result, Danish Defence and NIRAS, an engineering company, initiated an experiment to optimize the conditions for naturally occurring soil bacteria to break down soil contaminants.

Bacterial populations and the biodegradation of diesel compounds were continuously monitored by scientists from the University of Copenhagen's Department of Plant and Environmental Sciences and the Geological Survey of Denmark and Greenland (GEUS). After five years, the researchers found that the bacteria had bioremediated as much as 82 percent of the 5,000 tons of contaminated soil.

"The bacteria have proven extremely effective at breaking down the vast majority of the diesel compounds. As such, this natural method can be applied elsewhere in the Arctic, where it would otherwise be incredibly resource-intensive to remove contaminated soil by way of aircraft or ship," explains Professor Jan H. Christensen of the University of Copenhagen's Department of Plant and Environmental Sciences. Christensen has been responsible for analyzing the chemical fingerprints in the diesel-contaminated soil.

Never thoroughly studied and documented

The method, known as landfarming, is most often associated with warmer climates around the world. Prior to this project, landfarming had never been tested on a large scale under Arctic conditions. Nor had the method ever been as thoroughly studied and documented as in this experiment.

Landfarming works by distributing contaminated soil in a thin layer, which is then ploughed, fertilized and oxygenated every year to optimize conditions for bacteria to degrade hydrocarbons.

Watering the field

Landfarming works by distributing contaminated soil in a thin layer, which is then ploughed, fertilized and oxygenated every year to optimize conditions for bacteria to degrade hydrocarbons. Photo: Anders Christian Vestergaard

According to Anders Risbjerg Johnsen,a microbiologist and senior research scientist at GEUS, the landfarming work resulted in regular explosions of soil bacteria, which he was able to keep track of from Denmark using advanced samples of soil bacteria.

"Having a wide variety of hydrocarbon-degrading bacteria is essential as the 10,000 various diesel compounds contaminating the soil require different degradation pathways to be broken down," explains Johnsen.

Ability to clean up abandoned bases

Warmer "summer" temperatures of between 0 and 10 degrees only last about three months in Mestersvig. For the rest of the year, the soil is frozen. Thus, it was uncertain whether Greenlandic soil bacteria could break down the leaked diesel as effectively as bacteria in warmer conditions.

Fortunately, the study demonstrated that the bacteria could easily degrade diesel contaminants in the soil, despite the frigid temperatures. In the future, the researchers hope that naturally occurring bacteria can be used to remediate contamination in the Greenlandic environment at roughly 30 other deserted installations. The lack of infrastructure has made it extremely expensive and resource-intensive to move soil around as, for example, might be done in Denmark.

"Some degree of diesel pollution can be found at nearly every Arctic site where there was once a weather station, research station or military installation. It is likely that the approach used in our experiments can be used at many of these sites," say Jan H. Christensen and Anders Risbjerg Johnsen.

The researchers are returning to Greenland this year to conduct new studies on the experiment. They hope to find that the bacteria have successfully degraded all remaining diesel contamination.

The role of people infected with malaria without showing symptoms presents a hidden risk to efforts to control the disease after they were found to be responsible for most infections in mosquitoes, according to a study published in The Lancet Infectious Diseases.

Researchers from the Infectious Diseases Research Collaboration (IDRC), London School of Hygiene & Tropical Medicine (LSHTM), Radboud university medical center and University of California, San Francisco, found asymptomatic children in the Uganda study were the biggest source of malaria parasites transmitted to mosquitoes. This could provide a new opportunity for control efforts by targeting this infectious reservoir.

Malaria presents a major health threat globally, with 94% of cases on the African continent alone, according to the WHO World Malaria Report 2020. The disease is passed to a human through the bite of an infected female Anopheles mosquito causing infection with the parasite. The predominant and most deadly parasite, Plasmodium falciparum, accounts for over 75% of mortality worldwide and is highly prevalent in Uganda.

Malarial parasites depend on a life cycle in which they constantly move back and forth between humans and mosquitoes. Successfully interrupting transmission of the disease can involve clearing parasites from human 'hosts' using anti-malaria drugs.

Nagongera sub-county (Tororo district) in eastern Uganda has historically very high malaria transmission but following intensive malaria control efforts, such as insecticide-treated bednets, indoor residual spraying (IRS) with insecticides and access to malaria drugs, infections - or at least symptomatic cases - have gone down remarkably.

The research team aimed to investigate patterns of malaria infection and understand more about transmission in the area. The study involved two years of regularly testing more than 500 people for evidence of malaria parasites. The genetic make-up of parasites was determined, as well as their ability to infect mosquitoes.

The researchers found that individuals who were asymptomatic were unknowingly responsible for most mosquito infections in the study. People with symptomatic infections were responsible for less than 1% of mosquito infections and appeared to play a negligible role in sustaining transmission.

School-aged children aged 5-15 years were responsible for over half (59%) of the infectious reservoir, followed by the under-5s (26%) and people aged 16 years and older (16%). Surprisingly, the researchers found just four children were linked to 60% of the infected mosquitoes studied.

Co-author Dr John Rek from IDRC said: "These findings are a real eye opener in the fight against malaria. We found that infections in school-aged children drive malaria transmission. Some children harboured billions of malaria parasites in their bloodstream without experiencing symptoms."

LSHTM co-author Professor Sarah Staedke said: "School-aged children are an important reservoir of malaria parasites that could be easily targeted for control interventions, such as chemoprevention through intermittent preventive treatment.

"This would benefit individual children, may reduce malaria transmission, and could help sustain malaria gains if intense vector control measures are interrupted."

Understanding transmission among asymptomatic cases is particularly important in areas where malaria control has been successful, but there is a risk that malaria might resurge when control measures are relaxed or withdrawn. Asymptomatic children that keep malaria circulating at relatively low levels could be sufficient to cause infections to quickly rebound if control efforts are not maintained. In other parts of Uganda, when intense malaria control with indoor residual spraying was halted, infections rebounded within weeks.

Principal author Professor Teun Bousema, from Radboud university medical center, said: "Our study demonstrates that even when malaria appears under control, there is a reservoir of infected individuals who can sustain the spread of this deadly disease. Unless their infections are targeted, malaria can quickly return."

Overall, these findings provide evidence that asymptomatic infections are an important source of onward transmission to mosquitoes. Many malaria infections that contribute to transmission are initially below the level detectable by conventional diagnostic tests, including microscopy and rapid diagnostic tests.

Professor Moses Kamya, IDRC co-author of the study, said: "Only through focused interventions, ideally supplemented by highly sensitive testing, can we target the reservoirs of infection in school-age children."

The study authors acknowledge limitations of the study including the length of time between participant sample selection and mosquito feeds, meaning they did not routinely measure infectiousness in the first few weeks of asymptomatic infections. They also noted that trial participants had exceptionally good access to care whereas in other settings people with symptomatic malaria infections might develop more transmissible infections if treatment is not administered quickly.

Several different causes of ageing have been discovered, but the question remains whether there are common underlying mechanisms that determine ageing and lifespan. Researchers from the Max Planck Institute for Biology of Ageing and the CECAD Cluster of Excellence in Ageing research at the University Cologne have now come across folate metabolism in their search for such basic mechanisms. Its regulation underlies many known ageing signalling pathways and leads to longevity. This may provide a new possibility to broadly improve human health during ageing.

In recent decades, several cellular signalling pathways have been discovered that regulate the lifespan of an organism and are thus of enormous importance for ageing research. When researchers altered these signalling pathways, this extended the lifespan of diverse organisms. However, the question arises whether these different signalling pathways converge on common metabolic pathways that are causal for longevity.

The search begins in the roundworm

The scientists started their search in the roundworm Caenorhabditis elegans, a well-known model organism for ageing research. "We studied the metabolic products of several, long-lived worm lines. Our analyses revealed that, among other things, we observed clear changes in the metabolites and enzymes of the folate cycle in all worm lines. Since folate metabolism plays a major role in human health, we wanted to further pursue its role in longevity", explains Andrea Annibal, lead author of the study.

A common mechanism for longevity

Folates are essential vitamins important for the synthesis of amino acids and nucleotides - the building blocks of our proteins and DNA. "We tuned down the activity of specific enzymes of folate metabolism in the worms. Excitingly, the result was an increase in lifespan of up to 30 percent", says Annibal. "We also saw that in long-lived strains of mice, folate metabolism is similarly tuned down. Thus, the regulation of folate metabolism may underlie not only the various longevity signalling pathways in worms, but also in mammals."

"We are very excited by these findings because they reveal the regulation of folate metabolism as a common shared mechanism that affects several different pathways of longevity and is conserved in evolution", adds Adam Antebi, director at the Max Planck Institute for Biology of Ageing. "Thus, the precise manipulation of folate metabolism may provide a new possibility to broadly improve human health during ageing." In future experiments, the group aims to find out the mechanism by which the folate metabolism affects longevity.

In an international study published by the journal Environment International, the University of Surrey led an international team of air pollution experts in monitoring pollution hotspots in 10 global cities: Dhaka (Bangladesh); São Paulo (Brazil); Guangzhou (China); Medellín (Colombia); Cairo (Egypt); Addis Ababa (Ethiopia); Chennai (India); Sulaymaniyah (Iraq); Blantyre (Malawi); and Dar-es-Salaam (Tanzania).

Surrey's Global Centre for Clean Air Research (GCARE) set out to investigate whether the amount of fine air pollution particles (PM2.5) drivers inhaled is connected to the duration drivers spend in pollution hotspots and socio-economic indicators such as gross domestic product (GDP).

Across all the cities in the study, researchers found that drivers only needed to spend a short amount of time in high-pollution hotspots to inhale a significant amount of PM2.5 particles. For example, drivers in Guangzhou and Addis Ababa spent 26 and 28 per cent of their commute in hotspot areas, which contributed to 54 and 56 per cent of the total amount of air pollution inhaled on their trip.

The researchers found that the cities where drivers were exposed to the highest levels of PM2.5 pollution - Dar-es-Salaam, Blantyre and Dhaka - also experienced higher death rates per 100,000 commuting car population per year. The low PM2.5 levels in Medellín, São Paulo and Sulaymaniyah corresponded with very low death rates.

The international study assessed economic losses by measuring a city's death rate caused by PM2.5 car exposure against its GDP per capita. It found that, for most cities, lower GDP linked directly to more significant economic losses caused by in-car PM2.5 exposure - with Cairo and Dar-es-Salaam being impacted the most (losses of 8.9 and 10.2 million US dollars per year, respectively).

The team also found that, except for Guangzhou, cities with higher GDP per capita have less hotspot areas during an average route trip, thus decreasing the risk to drivers.

Professor Prashant Kumar, Principal Investigator of CArE-Cities Project, Associate Dean (International) and Founding Director of GCARE at the University of Surrey, said: "Our global collaborative project has confirmed that air pollution disproportionately affects developing countries. Many countries are caught in a vicious cycle where their low GDP leads to higher pollution exposure rate for drivers, which leads to poorer health outcomes, which further damages the economy of those cities. This is discouraging news - but it should galvanise the international community to find and deploy measures that mitigate the health risks faced by the world's most vulnerable drivers."

Professor Shi-Jie Cao, a collaborative partner from the Southeast University, said: "If we are ever to make a world where clean air is available to all, it will take a truly global collaborative effort - such as CArE-Cities. We hope to continue to work closely with Surrey and other global partners, sharing knowledge and expertise that will make a cleaner future a reality."

Professor Adamson Muula, a collaborative partner from formerly University of Malawi and now Head of Public Health at the Kamuzu University of Health Sciences (KUHeS), said: "If developing countries are to not be left behind in the struggle against air pollution and climate change, it is important that we build the capacity and knowledge to gather on-the-ground data. This project is a small but a significant step in the right direction for Malawians; a direction which will lead to better decisions and cleaner air for Malawi."

Our eyes move three times per second. Every time we move our eyes, the world in front of us flies across the retina at the back of our eyes, dramatically shifting the image the eyes send to the brain; yet, as far as we can tell, nothing appears to move. A new study provides new insight into this process known as "visual stabilization". The results are published in the Proceedings of the National Academy of Sciences.

"Our results show that a framing strategy is at work behind the scenes all the time, which helps stabilize our visual experience," says senior author Patrick Cavanagh, a research professor in psychological and brain sciences at Dartmouth and a senior research fellow in psychology at both Glendon College and the Centre for Vision Research at York University. "The brain has its own type of steadycam, which uses all sorts of cues to stabilize what we see relative to available frames, so that we don't see a shaky image like we do in handheld movies taken with a smartphone. The visual world around us is the ultimate stable frame but our research shows that even small frames work: the locations of a test within the frame will be perceived relative to the frame as if it were stationary. The frame acts to stabilize your perception."

One such example is when someone waves goodbye to you from the window of a moving bus. Their hand will appear as if it's moving up and down relative to the window rather following the snake-like path that it actually traces out from the moving bus. The bus window acts like a frame through which the motion of the hand waving good-bye is seen relative to that frame.

The study consisted of two experiments that tested how a small square frame moving on a computer monitor affected participants' judgments of location. The experiments were conducted in-person: eight individuals including two of the authors; and also online due to the COVID-19 pandemic: 274 participants were recruited from York University of which 141 had complete data. The data were very similar for both types of participants.

In Experiment 1, a white, square frame moves left and right, back and forth, across a grey screen and the left and right edges of the square flash when the square reaches the end of its path: the right edge flashes blue at one end of the travel and the left edge flashes red at the other, as shown in the figure. Participants were asked to adjust a pair of markers at the top of the screen to indicate the distance they saw between the flashed edges. Experiment 1 had two conditions. The first condition, demonstrated in Movie 1, evaluated how far apart the outer left and right edges of the square frame appeared. In this example, the frame travel is longer than the frame size so the red flash is physically to the left of the blue flash. When the frame is moving slowly at the start, we see the flashes where they really are, with red to the left. However, once the frame is moving fast enough, blue is seen left of red. This is where they would be, if the frame were actually stationary. The moving frame fools us by stabilizing our judgments of location. Further on in the movie, the frame briefly fades out to reveal that the red flash is actually to the left of the blue flash, which has been the case the entire time.

The second condition assessed the travel of the frame's physical edge. The left edge flashes at each end of the frame's travel and the distance the frame travels is seen as the space between the two flashes.

The data from both conditions of Experiment 1 demonstrated that participants perceived the flashed edges of the frame as if it were stable even though it was clearly moving, illustrating what the researchers call the "paradoxical stabilization" produced by a moving frame.

Experiment 2 again demonstrated the stabilizing power of a moving frame (see Movie 2)) by flashing a red disc and a blue disc at the same location within a moving frame. The square frame moves back and forth from left to right while the disc flashes red and blue in alternation. As in Experiment 1, participants were asked to indicate the perceived separation between the red and blue discs. Even though there is no physical separation between the discs, the moving frame creates the appearance that the two discs are located to the left and right of their true locations, relative to the frame where they flashed. In other words, participants perceived the location of the discs relative to the frame, as if it were stationary and this was true across a wide range of frame speeds, sizes, and path lengths.

"By using flashes inside a moving frame, our experiments triggered a paradoxical form of visual stabilization, which made the flashes appear in positions where they were never presented," says Cavanagh. "Our results demonstrate a 100% stabilization effect triggered by the moving frames - the motion of the frame has been fully discounted. These data are the first to show a frame effect that matches our everyday experience where, each time our eyes move, the motion of the scene across our retinas has been fully discounted making the world appear stable."

"In the real-world, the scene in front of us acts as the anchor to stabilize our surroundings," Cavanagh says. Discounting the motion of the world as our eye move makes a lot of sense, as most scenes (i.e. house, workplace, school, outdoor environment) are not moving, unless an earthquake is occurring.

"Every time our eyes move, there's a process that blanks out the massive blur caused by the eye movement. Our brain stitches this gap together so that we don't notice the blank, but it also uses the motion to stabilize the scene. The motion is both suppressed and discounted so that we can keep track of the location of objects in the world," says Cavanagh.

Based on the study's results, the research team plans to explore visual stabilization further using brain imaging at Dartmouth.

Corticosteroids may be an effective treatment for children who develop a rare but serious condition after COVID-19 infection.

This is the finding of an international study of 614 children, published in the New England Journal of Medicine, led by Imperial College London.

All children in the study developed a serious disorder following COVID-19 infection. This condition, called multi-system inflammatory syndrome in children (MIS-C), is thought to affect 1 in 50,000 children with SARS-CoV-2 infection.

The new disorder, which is also called paediatric inflammatory multi-system syndrome temporally associated with SARS-CoV-2 infection (PIMS-TS), affects children of all ages but is more common in older children and teenagers. The disorder generally occurs 2-6 weeks after infection with the SARS-CoV-2 virus.

The illness is characterised by persistent high fever, often accompanied by abdominal pain, vomiting, red eyes and red rash. Severely affected children have developed heart inflammation, with shock and failure of multiple organs.

Fortunately, with optimal treatment the majority of affected children have recovered well. However, worldwide most reports suggest a fatality rate of 2-4%.

An important concern has been that some affected children have developed inflammation of their arteries that supply the heart with blood (called coronary arteries), resulting in widening of these arteries. This is also known to happen in another condition called Kawasaki disease.

The new study, supported by the EU's Horizon 2020 programme, investigated two initial treatments for this condition: a type of steroid called corticosteroids (such as methyl prednisolone) and antibody treatment (called immunoglobulin). The antibodies come from human blood, and have been shown to reduce inflammation in the body. The study also compared initial treatment with steroids together with immunoglobulin.

The study involved hundreds of doctors worldwide uploading information about patient outcomes onto an online database, and was not a randomised controlled trial (see Notes to Editors).

All three treatments (immunoglobulin, immunoglobulin combined with corticosteroids and cortico-steroids alone) resulted in more rapid resolution of inflammation, as measured by the level of a protein that indicates inflammation levels in the body, called C-reactive protein (CRP).

The CRP fell by half approximately one day quicker in those receiving treatment. There were no clear differences between the three treatments in rate of recovery from organ failure, or progression to organ failure.

The number of fatal cases (2%) was too low to enable comparison between treatments, but death was included in a combined assessment with organ failure, which found no significant differences between the three treatments.

However, when analysis was restricted to the 80% of children who met the World Health Organization's criteria for MIS-C, there was evidence of a lower rate of organ support or death at 2 days in those receiving steroids alone as initial treatment, compared to immunoglobulin alone.

Dr Elizabeth Whittaker, one of the authors of the study from Imperial's Department of Infectious Disease, and one of the first doctors in the world to originally identify this condition, together with colleagues at Imperial College and Imperial College Healthcare NHS Trust, said: "The finding that outcome is similar for patients treated with steroids alone as with those treated with steroids and immunoglobulin or immunoglobulin alone, suggests that steroids may be a cheaper and more available alternative to immunoglobulin. Corticosteroids are cheap and available worldwide whereas immunoglobulin is expensive, and there is a worldwide shortage of it. This is a particular problem in many low and middle income countries. "

However the authors stress there is insufficient data to establish that all three treatments are equivalent in preventing coronary artery aneurysms. Around 6 per cent of children in the study suffered a coronary artery aneurysm.

Professor Michael Levin, from the Department of Infectious Disease at Imperial, who led the study, said: "The study has been a real example of international collaboration and the willingness of paediatricians in many countries to share their data and experience to enable important questions as to optimal treatment to be answered. Our finding, that treatments with immunoglobulin, steroids or a combination of both agents all result in more rapid resolution of inflammation (and have similar rates of progression to organ failure or recovery from critical illness), will be of great value to paediatricians worldwide in their treatment of children with this new disorder. As immunoglobulin is unavailable or in short supply in many countries, and is expensive, the findings of this study may provide some reassurance for those who only have access to corticosteroids, particularly in those countries with more limited resources.

However it is important to note that our study does not yet provide a definitive answer as to whether any of the treatments lowers the risk of coronary artery aneurysms, as the numbers with this complication were too low. The study is continuing to enrol patients and our planned further analysis with larger numbers of patients should provide answers to this question."

Olives, well-known for their characteristic bitter taste, are in high demand owing to the popularity of the oil that's derived from them. The health benefits of olive oil are well known, ranging from antiviral, anti-cancer, to even anti-hypertensive effects. These benefits are attributed to "oleuropein," the most abundant olive secoiridoid found in olives.

An efficient method to enhance the quality of plant products is by using molecular methods to manipulate their genes and enhancing their yield. With olives, however, this is still a challenge, because of a lack of sufficient genome data.

So far, the genomes of two European olive varieties have been sequenced. But to fully decipher the sequence composition of the genetic material, computationally assembling these genomes is essential. This has been difficult to do with olives, owing to the high number of repetitive sequences in their genomes and their complex nature.

A team of scientists from China, led by Dr. Guodong Rao, sought to address this challenge by using the latest sequencing technologies to assemble these genomes. Dr. Rao explains, "In our study, a chromosome level high-quality olive genome was obtained, which largely improved the previous version of the genomes." Their study has been published in Horticulture Research.

For their study, the scientists first collected European olive leaf samples and extracted their DNA. Then, they used advanced sequencing technologies called "Oxford Nanopore third-generation sequencing" and "Hi-C" to obtain the sequences and performed seven different strategies to assemble the final genome. The final genome that they obtained underwent phylogenetic analysis and comparisons with other related species of plants.

The team's findings led to the successful identification of nine gene families with 202 genes involved in the biosynthesis of oleuropein, which is twice as many as were known until now! The scientists also revealed that a part of olive DNA is similar to that of soybean and sunflower. They found olives are genetically closest to the oleaster plant, also called the Russian olive.

Dr. Rao highlights the applications of this study, "Through the high-quality genome map we determined, it is possible to cultivate olive varieties and olive oil of higher quality in the future."

Hopefully, this research will find its way in olive breeding soon!

CHAPEL HILL, NC - UNC School of Medicine scientists led a collaboration of researchers to demonstrate a potentially powerful new strategy for treating cystic fibrosis (CF) and potentially a wide range of other diseases. It involves small, nucleic acid molecules called oligonucleotides that can correct some of the gene defects that underlie CF but are not addressed by existing modulator therapies. The researchers used a new delivery method that overcomes traditional obstacles of getting oligonucleotides into lung cells.

As the scientists reported in the journal Nucleic Acids Research, they demonstrated the striking effectiveness of their approach in cells derived from a CF patient and in mice.

"With our oligonucleotide delivery platform, we were able to restore the activity of the protein that does not work normally in CF, and we saw a prolonged effect with just one modest dose, so we're really excited about the potential of this strategy," said study senior author Silvia Kreda, PhD, an associate professor in the UNC Department of Medicine and the UNC Department Biochemistry & Biophysics, and a member of the Marsico Lung Institute at the UNC School of Medicine.

Kreda and her lab collaborated on the study with a team headed by Rudolph Juliano, PhD, Boshamer Distinguished Professor Emeritus in the UNC Department of Pharmacology, and co-founder and Chief Scientific Officer of the biotech startup Initos Pharmaceuticals.

About 30,000 people in the United States have CF, an inherited disorder in which gene mutations cause the functional absence of an important protein called CFTR. Absent CFTR, the mucus lining the lungs and upper airways becomes dehydrated and highly susceptible to bacterial infections, which occur frequently and lead to progressive lung damage.

Treatments for CF now include CFTR modulator drugs, which effectively restore partial CFTR function in many cases. However, CFTR modulators cannot help roughly ten percent of CF patients, often because the underlying gene defect is of the type known as a splicing defect.

CF and splicing defects

Splicing is a process that occurs when genes are copied out - or transcribed - into temporary strands of RNA. A complex of enzymes and other molecules then chops up the RNA strand and re-assembles them, typically after deleting certain unwanted segments. Splicing occurs for most human genes, and cells can re-assemble the RNA segments in different ways so different versions of a protein can be made from a single gene. However, defects in splicing can lead to many diseases - including CF when CFTR's gene transcript is mis-spliced.

In principle, properly designed oligonucleotides can correct some kinds of splicing defects. In recent years the U.S. Food and Drug Administration has approved two "splice switching oligonucleotide" therapies for inherited muscular diseases.

In practice, though, getting oligonucleotides into cells, and to the locations within cells where they can correct RNA splicing defects, has been extremely challenging for some organs.

"It has been especially difficult to get significant concentrations of oligonucleotides into the lungs to target pulmonary diseases," Kreda said.

Therapeutic oligonucleotides, when injected into the blood, have to run a long gauntlet of biological systems that are designed to keep the body safe from viruses and other unwanted molecules. Even when oligonucleotides get into cells, the most usually are trapped within vesicles called endosomes, and are sent back outside the cell or degraded by enzymes before they can ever do their work.

A new delivery strategy

The strategy developed by Kreda, Juliano, and their colleagues overcomes these obstacles by adding two new features to splice switching oligonucleotides: Firstly, the oligonucleotides are connected to short, protein-like molecules called peptides that are designed to help them to distribute in the body and get into cells. Secondly, there is a separate treatment with small molecules called OECs, developed by Juliano and Initos, which help the therapeutic oligonucleotides escape their entrapment within endosomes.

The researchers demonstrated this combined approach in cultured airway cells from a human CF patient with a common splicing-defect mutation.

"Adding it just once to these cells, at a relatively low concentration, essentially corrected CFTR to a normal level of functioning, with no evidence of toxicity to the cells," Kreda said.

The results were much better with than without OECs, and improved with OEC dose.

There is no mouse model for splicing-defect CF, but the researchers successfully tested their general approach using a different oligonucleotide in a mouse model of a splicing defect affecting a reporter gene. In these experiments, the researchers observed that the correction of the splicing defect in the mouse lungs lasted for at least three weeks after a single treatment - hinting that patients taking such therapies might need only sporadic dosing.

The researchers now plan further preclinical studies of their potential CF treatment in preparation for possible clinical trials.